Am. J. Respir. Crit. Care Med., Vol 154, No. 1, Jul 1996, 244-246.
Prejunctional inhibition of cholinergic responses by prostaglandin E2 in human bronchi
JL Ellis and ND Conanan
Division of Clinical Immunology, John Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224-6801, USA.
The effect of prostaglandin E2 (PGE2) on cholinergic responses elicited by
electrical field stimulation (EFS) (8 Hz, 1 ms, 8 V for 10 s every 100 s)
of human isolated human bronchi was studied. Indomethacin (1 microM) was
found to produce approximately a 100% increase in the cholinergic response.
In the presence of indomethacin, PGE2 (1-300 nM) was found to
concentration-dependently inhibit the cholinergic responses to EFS. A
maximal inhibition was obtained with 100 nM PGE2 which produced an 80%
inhibition of the cholinergic response. By contrast 100 nM PGE2 was without
significant effect on the concentration response curve to exogenously added
acetylcholine. The inhibitory effect of PGE2 on the EFS-induced cholinergic
responses was not modified by the large conductance Ca(2+)-activated K+
channel inhibitor charybdotoxin (100 nM). These results suggest that
endogenously released prostaglandins, presumably PGE2, act to inhibit
cholinergic responses by a prejunctional mechanism in human isolated
bronchi. In contrast to other autocoids, this inhibition does not involve
the activation of large-conductance Ca(2+)-activated K+ channels.
